With all due respect, the expert opinions at other big Pharma's did not help. We only have to look at Pfizer, J&J Eli Lilly Million dollar efforts in Alzheimer’s research to know they can be worng.
Novartis AG plans to ramp up its research in Alzheimer’s disease, a potential $20 billion market lacking a major contender and littered with three high-profile drug failures in the past year alone.
“This remains high on our radar, with high unmet medical need,” Tim Wright, who heads the Basel, Switzerland-based company’s drug development, said on a conference call arranged by Sanford C. Bernstein & Co. analyst Tim Anderson in April. Novartis didn’t respond to a request for comment on its Alzheimer’s research.
Novartis would be racing to catch up with Roche Holding AG (ROG) and Merck & Co. (MRK), which are conducting human tests on treatments for Alzheimer’s, the most common dementia illness. Drugmakers are vying to find a way to slow the disease, which may affect 65 million people by 2030. The field is marked with failures, including a study Baxter International Inc. (BAX) released this month in which its Gammagard drug didn’t help patients.
“Should Novartis move into Alzheimer’s? Yes,” Michael Leuchten, an analyst at Barclays Plc in London, said by phone. “Will it be easy to do? No.”
Novartis is pursuing alternatives including licensing agreements, Wright said on the call. So far the drugmaker’s development in the area hasn’t progressed as quickly as Novartis hoped over past years, he said.
Novartis sells Exelon, a drug that lessens symptoms of the disease by preventing the breakdown of a substance linked to learning and memory. The drug, also used in Parkinson’s disease, may have about $930 million in sales this year, according to analysts’ estimates compiled by Bloomberg. Novartis bought a license to an Alzheimer’s vaccine from Cytos Biotechnology AG in 2003, and the companies completed a mid-stage trial in December.
“Alzheimer’s would really make a lot of sense for Novartis,” Olav Zilian, an analyst at Helvea SA in Geneva, sai
Molecular probe agent, simultaneously in the live mouse. This new revolutionary technology is expected to offer new insights into the relationships between bio-metal elements and associated bio molecules, and the roles they play in diseases such as diabetes and cancer.
Motomura, S. et al. Improved imaging performance of semiconductor Compton camera GREI makes for a new methodology to integrate bio-metal analysis and molecular imaging technology in living organisms, Journal of Analytical Atomic Spectrometry,
Motomura, S. et al. Improved imaging performance of semiconductor Compton camera GREI makes for a new methodology to integrate bio-metal analysis and molecular imaging technology in living organisms, Journal of Analytical Atomic Spectrometry, 2013.,doi: 10.1039/C3JA30185K
Metal elements and molecules interact in the body but visualizing them together has always been a challenge. Researchers from the RIKEN Center for Life Science Technologies have developed a new molecular imaging technology that enables them to visualize bio-metals and bio-molecules simultaneously in a live mouse. This new technology will enable researchers to study the complex interactions between metal elements and molecules Metal elements and molecules interact in the body but visualizing them together has always been a challenge. Researchers from the RIKEN Center for Life Science Technologies have developed a new molecular imaging technology that enables them to visualize bio-metals and bio-molecules simultaneously in a live mouse. This new technology will enable researchers to study the complex interactions between metal elements and molecules in living organisms.
Metal elements such as zinc, iron and copper are present in trace amounts in the body and play an important role in myriad biological processes including gene expression, signal transduction and metabolic reactions. Abnormalities in the behaviour of these elements often reflect abnormalities in associated bio-molecules and studying them together can offer great insight into many biological
Dr. Shuichi Enomoto, Dr. Shinji Motomura and colleagues, from the RIKEN Center for Life Science Technologies have developed a gamma-ray imaging camera enabling them to detect the gamma-rays emitted by multiple bio-metal elements in the body and study their behavior.
Their second prototype of the system, called GREI–II and presented today in the Journal of Analytical Atomic Spectrometry, enables them to visualize multiple bio-metal elements more than 10 times faster than before, and to do so simultaneously with positron emission tomography (PET).
In the study, the researchers were able to visualise two radioactive agents injected in a tumor-bearing mouse, as well as an anti-tumor antibody labelled with a PET
The Salk Institute for Biological Studies also came out with news on a mouse study that J147, reverses memory deficits and slows Alzheimer's disease. There was another company made the same claim last week but PBT2 is the only drug I know that has seen improvement in a human trial. All this news could be speeding up interest in Prana.
In my opnion this Scientific America article this supports PBT's 2 technolology.
A Nobel Prize–winning discovery found that mad cow and related infectious diseases occur when aberrant proteins—prions—wreak havoc by causing normal versions of those proteins to become malformed.
Prionlike disease processes also appear to be at work in major neurodegenerative disorders, including Alzheimer's, Parkinson's and Lou Gehrig's, although they are not transmitted from person to person.
How proteins contort into a form that causes others to undergo a similar transformation may lead to new approaches to preventing and treating some of the world's leading neurological illnesses.
A chain reaction of toxic proteins may help explain Alzheimer's, Parkinson's and other killers—an insight that could lead to desperately needed new treatment options
Under a microscope, a pathologist searching through the damaged nerve cells in a brain tissue sample from a patient who has died of Alzheimer's disease can make out strange clumps of material. They consist of proteins that clearly do not belong there. Where did they come from, and why are there so many of them? And most important, what do they have to do with this devastating and incurable disorder? The search for answers has turned up a startling discovery: the clumped proteins in Alzheimer's and other major neurodegenerative diseases behave very much like prions, the toxic proteins that destroy the brain in mad cow disease
Prions are misshapen yet durable versions of proteins normally present in nerve cells that cause like proteins to misfold and clump together, starting a chain reaction that eventually consumes entire brain regions. In the past 10 years scientists have learned that such a process may be at work not only in mad cow and other exotic diseases but also in major neurodegenerative disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (also known as ALS or Lou Gehrig's disease) and the concussion-related dementia of football players and boxers.
Thanks Kadash, I am hoping Prana releases the paper on PBT2 ability to stop the cognitive decline in a normal but aging brain. In the meantime I look forward to the results of the trials.
Furthermore, activating the NF-κB pathway led to a drop in the levels of gonadotropin-releasing hormone (GnRH), a neuron-generating chemical, and a subsequent decrease in the development of new neurons. GnRH is known to regulate reproductive processes, but seems also to be necessary for maintaining youthfulness, Cai said.
When the researchers injected GnRH into the hypothalamuses of mice, it promoted neuron generation and decelerated aging. The team gave daily GnRH injections to old mice over an extended period, finding that the treatment slowed cognitive decline due to aging.
Putting the brakes on aging
GnRH treatment represents a potential means of slowing the progress of aging or age-related diseases, the researchers say. Interfering with the immune response in the hypothalamus could also be a promising approach, Cai said, though he added that the GnRH treatment might be more practical given current technology.
Aging researcher Caleb Finch of University of Southern California Davis School of Gerontology, who was not involved in the work, called it a "brilliant study." Finch has previously argued that the hypothalamus contains "pacemakers" that control the rate of aging. The new study's approach showed a more modest increase in life span than approaches such as calorie restriction (which has been shown to extend life span in mice), Finch said. "Nonetheless, the case is now powerfully made for the role of the neuroendocrine mechanisms as modulators of aging."
Next, the researchers hope to gain a deeper understanding of the molecular function of the hypothalamus in controlling aging and life span. "There are a lot of details we don't know," Cai said, such as the other molecules that are involved. The team is ultimately interested in translating their work into clinical efforts to slow down aging.
The findings were reported online today (May 1) in the journal Nature.
The secret to living longer may be all in your head after all.
A team of neuroscientists has found a way to extend the lives of lab mice by simply switching a brain pathway on and off, according to a paper published May 1 in the journal Nature.
"If we just activated this pathway in the hypothalamus, it accelerated aging," study researcher Dongsheng Cai, of the Albert Einstein College of Medicine, told Business Insider. "If we inhibit this pathway, we can slow down aging. There were lots of assessments that showed inhibiting it led to an increase of lifespan by roughly 20%. So, that's pretty remarkable."
Aging and the brain
The scientists focused on the hypothalamus because it is the region in the brain responsible for growth and metabolism — two things that change as we age. Cai and colleagues have published previous papers on the role of the hypothalamus in age-related metabolic diseases like diabetes, hypertension, and obesity.
But Cai felt that the information on what actually causes aging was lacking. Aging has systemic effects on the body: hitting many different organs and causing many different diseases at once.
He thought that chemicals in the brain associated with age-related diseases, like metabolic syndromes and cancer, might also play a role in aging.
"Aging by itself is not a disease," Cai said, "but it is a risk factor for many diseases. It is more like a ground for the development of many epidemic diseases like diabetes and neurodegenerative disorders."
Stress and inflammation
In mice, the researchers experimented with a protein complex involved in inflammation in the hypothalamus called NF-kB. Inflammation is an overreaction of our body's immune system in response to stress. Inflammation can help heal and fight disease, but too much inflammation can be dangerous.
They were surprised by how much of an impact turning off NF-kB in the hypothalamus had on how long the mice lived — about 20% longer. On the flip side, turning it to overdrive accel
Take a look the methodishealth site and search Tanzi and look at handout Molecular and Genetic Basis of Alzheimer's Disease.
Rudy's new study.
Mass. General study finds protective gene variant promotes clearance of toxic amyloid beta protein from the brain
Massachusetts General Hospital (MGH) investigators have determined that one of the recently identified genes contributing to the risk of late-onset Alzheimer's disease regulates the clearance of the toxic amyloid beta (A-beta) protein that accumulates in the brains of patients with the disease. In their report receiving advance online publication in Neuron, the researchers describe a protective variant of the CD33 gene that promotes clearance of A-beta from the brain. They also show that reducing expression of CD33 in immune cells called microglia enhances their ability to clear away A-beta protein, raising the possibility that blocking CD33 activity could help the brain's immune system remove A-beta.
"Our findings show, for the first time, a "switch" that controls how fast microglial cells can clear A-beta protein from the brain as we age – CD33 is the key," says Rudolph Tanzi, PhD, director of the Genetics and Aging Unit in the MGH Department of Neurology and senior author of the Neuron paper. "If we can find a way of safely inactivating CD33 on microglia, we should be able to slow the accumulation of A-beta in aging brains and hopefully reduce risk for Alzheimer's disease."
In 2008, as part of the Alzheimer's Genome Project, Tanzi's team identified four novel genes containing variants that increased the risk of late-onset Alzheimer's, the most common form of the devastating neurological disorder. One of these was CD33. The protein was known to play a role in regulation of the innate immune system – the body's first line of defense against infection – but how it might function in the brain and possibly contribute to Alzheimer's risk was not known.
In the current study, the researchers first found that CD33 activity was significantly higher in microglia cells in brain samples from Alzh
A lot of interresting information coming out of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing. Also saw a paper where they recruited patients from the study to check for plaque in the retina.
Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort stud
La Jolla, CA (Scicasts) – What is it about the extra chromosome inherited in Down syndrome―chromosome 21―that alters brain and body development?
Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have new evidence that points to a protein called sorting nexin 27, or SNX27. SNX27 production is inhibited by a molecule encoded on chromosome 21.
The study, published March 24 in Nature Medicine, shows that SNX27 is reduced in human Down syndrome brains. The extra copy of chromosome 21 means a person with Down syndrome produces less SNX27 protein, which in turn disrupts brain function. What's more, the researchers showed that restoring SNX27 in Down syndrome mice improves cognitive function and behaviour.
"In the brain, SNX27 keeps certain receptors on the cell surface―receptors that are necessary for neurons to fire properly," said Dr. Huaxi Xu, professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging and Stem Cell Research Center and senior author of the study. "So, in Down syndrome, we believe lack of SNX27 is at least partly to blame for developmental and cognitive defects."
SNX27's role in brain function
Xu and colleagues started out working with mice that lack one copy of the snx27 gene. They noticed that the mice were mostly normal, but showed some significant defects in learning and memory. So the team dug deeper to determine why SNX27 would have that effect. They found that SNX27 helps keep glutamate receptors on the cell surface in neurons. Neurons need glutamate receptors in order to function correctly. With less SNX27, these mice had fewer active glutamate receptors and thus impaired learning and memory.
SNX27 levels are low in Down syndrome
Then the team got thinking about Down syndrome. The SNX27-deficient mice shared some characteristics with Down syndrome, so they took a look at human brains with the condition. This confirmed the clinical significance of their laboratory findings―humans with Down syndrome have significantly lower levels of SNX27.
Next, Xu and colleagues wondered how Down syndrome and low SNX27 are connected―could the extra chromosome 21 encode something that affects SNX27 levels? They suspected microRNAs, small pieces of genetic material that don't code for protein, but instead influence the production of other genes. It turns out that chromosome 21 encodes one particular microRNA called miR-155. In human Down syndrome brains, the increase in miR-155 levels correlates almost perfectly with the decrease in SNX27.
Xu and his team concluded that, due to the extra chromosome 21 copy, the brains of people with Down syndrome produce extra miR-155, which by indirect means decreases SNX27 levels, in turn decreasing surface glutamate receptors. Through this mechanism, learning, memory, and behaviour are impaired.
Restoring SNX27 function rescues Down syndrome mice
If people with Down syndrome simply have too much miR-155 or not enough SNX27, could that be fixed? The team explored this possibility. They used a noninfectious virus as a delivery vehicle to introduce new human SNX27 in the brains of Down syndrome mice.
"Everything goes back to normal after SNX27 treatment. It's amazing―first we see the glutamate receptors come back, then memory deficit is repaired in our Down syndrome mice," said Xin Wang, a graduate student in Xu's lab and first author of the study. "Gene therapy of this sort hasn't really panned out in humans, however. So we're now screening small molecules to look for some that might increase SNX27 production or function in the brain."
I think we are only seeing the tip of the iceberg on metals research making Pran's MPAC library very valuable in my opinion.
The Wellcome Trust-funded study entitled “A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport” by Florian Steinberg (1), Matthew Gallon (1), Mark Winfield (2), Elaine Thomas (1), Amanda J. Bell (1), Kate J. Heesom (3), Jeremy M. Tavaré (1) and Peter J. Cullen (1,4).
1. The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol.
2. School of Biological Sciences, University of Bristol.
3. Proteomics Facility, School of Biochemistry, University of Bristol, Bristol.
Researchers at the University of Bristol have revealed new insight into the function of a key protein attributed to impaired learning and memory in Down’s syndrome. The findings, published online in Nature Cell Biology, offer further molecular insight into how the reduced level of this key protein termed ‘sorting nexin-27’ [SNX27] may contribute to learning and memory problems associated with Down’s syndrome.
The Bristol-based team now reveal how SNX27 forms the core component of an ancient protein complex which functions to control the abundance of a select group of proteins at the surface of cells. Included among these proteins are numerous transporters that regulate the cell’s ability to take up various nutrients, including glucose and metal ions such as zinc and copper. In cells lacking SNX27, the level of these transporters is reduced and the cell’s ability to take up nutrients is adversely perturbed.
Peter Cullen, Professor of Biochemistry from the University’s School of Biochemistry and senior author of the Wellcome Trust-funded study, said: “Besides the previously recognised role of SNX27 in regulating the synaptic activity of neurones, our study suggests that the lack of SNX27 expression observed in Down’s syndrome may also lead to a reduced metabolic activity that may adversely affect neuronal development and cognitive function.
“Further analysis of the effect of reduced SNX27 expression on the synaptic and metabolic activity of specific neuronal populations will certainly provide much needed molecular insight into the complex neuropathology of Down’s syndrome as well as other neurological conditions.
As we have often talked about here, any use of PBT2 to help with cognition in a normal but aged brain would be the blockbuster of all drugs.